Molecular mechanisms of drug-induced thrombocytopenia (DITP). Drug- platelet-immunoglobulin interaction in DITP will be characterized, working from the hypothesis that drugs cause DITP by interacting with platelet membrane components to produce modifications recognized as immunogenic by certain sensitive individuals. Target molecules (and epitopes) recognized by platelet-specific antibodies. The structure of human platelet alloantigens will be determined by an approach already used to characterize the P1A1/P1A2 polymorphism of glycoprotein IIIa. Synthetic peptides corresponding to epitopes identified will be constructed and their ability to bind alloantibody determined. As a long-range goal, the use of such peptides to treat alloimmune disorders of platelets will be investigated. Pathogenesis of immune thrombocytopenias. New methods for detection of platelet-reactive immunoglobulins will be refined and used to improve understanding of the pathogenesis of neonatal alloimmune thrombocytopenic purpura, post-transfusion purpura, cyclic thrombocytopenic purpura, drug- induced thrombocytopenic purpura, and autoimmune thrombocytopenic purpura. Heterogeneity of human platelets: physiologic significance. Flow cytometry and other approaches will be used to identify changes associated with aging of platelets in the human circulation. Variable expression of class I HLA antigens on platelets will be further studied and the molecular biologic basis for this phenomenon examined. Findings made will be used to devise new strategies for transfusion therapy of alloimmunized patients. Optimum methods for short-term preservation of platelets at room temperature. Studies demonstrating that IgG and IgM accumulate on the membranes of stored platelets will be extended to determine whether these Ig are specific for platelet membrane modifications associated with storage and whether this phenomenon influences the recovery of transfused platelets.